The overarching goal of this program project is to build bridges across disciplines, linking higher cognitive functions to their underlying neurobiological bases and their molecular genetic underpinnings using a specific genetic disorder, Williams syndrome (WS). To accomplish this goal, the program combines cognitive, electrophysiological, structural and functional imaging, histological, with molecular genetic approaches to study groups of individuals with WS. The findings of peaks and valleys of abilities in WS, including mild to moderate mental retardation in the context of a specific deficit in visuospatial processing, relative strengths in face processing and certain aspects of language, in addition to hypersociability. This unique profile makes WS an invaluable paradigm for the study of brain and behavior relationships, and for mapping to the genome. Program project: Project II, Neurophysiological Imaging characterizes the electrophysiological signature of the WS brain during sensory and cognitive processing. Project III: Functional Neuroimaging, uses multifaceted imaging techniques (high field-structural, functional, and diffusion tensor imaging) to identify neural pathways involved in WS cognition. Project IV. Molecular and Cellular Architectonics, explores histological and gene expression differences within brain areas associated with the cognitive profile of WS. Project I: Neurocognitive Characterization, will examine cognitive processing mechanisms and map sources of cognitive variability to neural pathways and variations in genetic expression. Studies from each project work interactively using integrated approaches to test hypotheses related to dorsoventral and posterior/anterior gradients in brain development, as well as changes within limbic system pathways as they relate to cognition and behavior. Together, these studies provide new opportunities for illuminating pathways among specific genes, neural systems, and cognitive functions.